Scientists at the Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences report the development of a model of myocardial infarction using cardiomyocytes differentiated from human induced pluripotent stem cells. Their study “Development of a model of ischemic heart disease using cardiomyocytes differentiated from human induced pluripotent stem cells” appears in Biochemical and Biophysical Research Communications.
To date, laboratory animals such as mice have been used to model diseases including myocardial infarction. However, there have been concerns about the difference in characteristics of cardiomyocytes, e.g., heart rate and action of drugs, based on the difference of gene expression between laboratory animals and humans, according to Ken Takahashi, PhD, assistant professor in the university and lead author of the study.
Using this model, researchers can evaluate the extent of myocardial tissue damage by microscope morphologically, and by measuring injury-marker proteins and analyzing contractility and its synchroneity from recorded movies quantitatively, explained Takahashi. Further analysis revealed that gene expression of interleukin-8, an inflammation marker known to increase in acute myocardial infarction, increased in this model.
“Ischemic heart disease remains the largest cause of death worldwide. Accordingly, many researchers have sought curative options, often using laboratory animal models such as rodents. However, the physiology of the human heart differs significantly from that of the rodent heart,” the investigators wrote.
“In this study, we developed a model of ischemic heart disease using cardiomyocytes differentiated from human induced pluripotent stem cells (hiPS-CMs). After optimizing the conditions of ischemia, including the concentration of oxygen and duration of application, we evaluated the consequent damage to hiPS-CMs. Notably, exposure to 2% oxygen, 0 mg/mL glucose, and 0% fetal bovine serum increased the percentage of nuclei stained with propidium iodide, an indicator of membrane damage, and decreased cellular viability. These conditions also decreased the contractility of hiPS-CMs.
“Furthermore, ischemic conditioning increased the mRNA expression of IL-8, consistent with observed conditions in the in vivo heart. Taken together, these findings suggest that our hiPS-CM-based model can provide a useful platform for human ischemic heart disease research.”
“This myocardial infarction model will contribute to the development of preventive/therapeutic medicine more effective to humans even without sacrificing animals,” said Takahashi.
